Apparatus and semi-reflective optical system for carrying out analysis of samples

ABSTRACT

An optical disk for use in conducting an optical inspection of a biological, chemical or biochemical sample in association with an optical reader capable of scanning and reading optical disks with a beam of light has an optically transparent substrate having a semi-reflective layer which reflects a portion of the beam of light to form a reflected beam and transmits a portion of the beam of light to form a transmitted beam. The semi-reflective layer includes optically readable encoded information to be read by the reader for controlling the scanning of the reader relative the disk, the encoded information providing modulation of the reflected beam. The disk includes a sample support surface positioned to be scanned by the reader and on which the biological, chemical or biochemical sample may be located for optical inspection with the transmitted beam.

This application is a continuation of application Ser. No. 09/156,475,filed on Sep. 18, 1998; which is a continuation of application Ser. No.08/809,402, filed on Jul. 28, 1997, which is now U.S. Pat. No.5,892,577, issued on Apr. 6, 1999; which is a 371 of PCT/GB95/02186,filed Sep. 15, 1995; which claims priority from UK Patent ApplicationNo. 9418981.8 filed Sep. 21, 1994.

BACKGROUND OF THE INVENTION

The present invention relates to apparatus and to a method for carryingout optical analysis of samples and is applicable in particular to theanalysis of biological, chemical and biochemical samples

Many chemical, biochemical and biological assays rely upon inducing achange in the optical properties of a biological sample being tested.For example, in order to test for the presence of an antibody in a bloodsample, possibly indicating a viral infection, an enzyme-linkedimmunosorbent assay (ELISA) can be carried out which produces a visiblecoloured deposit if the antibody is present. An ELISA makes use of asurface which is coated with an antigen specific to the antibody to betested for. Upon exposure of the surface to the blood sample, antibodiesin the sample bind to the antigens. Subsequent staining of the surfacewith specific enzyme-conjugated antibodies and reaction of the enzymewith a substrate produces a precipitate which shows up the level ofantigen binding and hence allows the presence of antibodies in thesample to be identified. This identification is usually carried outusing a light microscope which allows an area of the substrate to beviewed by an operator.

In addition to colour staining using an ELISA, techniques such asfluorescence and gold labelling can be used to alter the opticalproperties of biological antigen material. Similar techniques are alsoused in

The present invention relates to apparatus and to a method for carryingout optical analysis of samples and is applicable in particular to theanalysis of biological, chemical and biochemical samples.

Many chemical, biochemical and biological assays rely upon inducing achange in the optical properties of a biological sample being tested.For example, in order to test for the presence of an antibody in a bloodsample, possibly indicating a viral infection, an enzyme-linkedimmunosorbent assay (ELISA) can be carried out which produces a visiblecoloured deposit if the antibody is present. An ELISA makes use of asurface which is coated with an antigen specific to the antibody to betested for. Upon exposure of the surface to the blood sample, antibodiesin the sample bind to the antigens. Subsequent staining of the surfacewith specific enzyme-conjugated antibodies and reaction of the enzymewith a substrate produces a precipitate which shows up the level ofantigen binding and hence allows the presence of antibodies in thesample to be identified. This identification is usually carried outusing a light microscope which allows an area of the substrate to beviewed by an operator.

In addition to colour staining using an ELISA, techniques such asfluorescence and gold labelling can be used to alter the opticalproperties of biological antigen material. Similar techniques are alsoused in general histology to visualise specific areas of tissue, e.g.particular cell types or cell structures, as well as in cell culture.

A significant disadvantage of existing optical analysis techniques isthat they are open to human error because of their subjective nature.These techniques are also not suited to uses where a high throughput ofsamples is required, for example in blood screening applications orcervical smear tests, and are thus relatively expensive to use. The costfactor is exacerbated because, more often than not, different equipmentis required for each particular technique.

An object of the present invention is to provide a technique forcarrying out the optical analysis of samples which overcomes or at leastmitigates certain of these disadvantages.

It is also an object of the present invention to provide an opticalanalysis technique which allows high speed automatic analysis ofbiological, biochemical and chemical samples and which is versatileenough to allow it to be used for a variety of different studies.

These objects are achieved by adapting the technology which has beendeveloped in the field of audio and video compact discs to scansurfaces, to which a sample has been attached, using a light beam whichis substantially focused onto that surface. A detector is arranged todetect light reflected from, or transmitted through that surface, and todetermine from analysis of the detected light whether the light beam hasbeen interfered with by the sample material.

According to a first aspect of the present invention there is provided amethod of conducting an optical inspection of a biological, chemical, orbiochemical sample, the method comprising the steps of;

supporting the sample on a substrate;

directing a beam of electromagnetic radiation from a radiation sourceonto the substrate;

scanning the beam over the substrate by rotating the substrate about anaxis substantially perpendicular to the substrate and by moving theradiation source in a direction having a component radial to said axis;and

detecting radiation reflected from and/or transmitted through thesubstrate and sample and providing an output signal corresponding to thedetected radiation.

According to a second aspect the present invention there is provided asystem for automatically carrying out an optical inspection of a sampleto determine whether or not the sample comprises material whichinterferes with incident electromagnetic radiation, the systemcomprising;

a substrate having a surface for supporting the sample;

a source of electromagnetic radiation for providing a beam ofelectromagnetic radiation;

means for scanning said beam across said surface of the substrate; and

detector means which in use is arranged to detect electromagneticradiation reflected from and/or passing through the substrate and thesample, the substrate being provided with distributed electromagneticradiation modulating means for modulating at least a part of said beamwith a digitally encoded position address indicative of the location onsaid surface on which the beam is currently directed, the detector meansbeing arranged to decode the modulated electromagnetic radiation beam todetermine the encoded address and to determine if the received beam hasbeen modulated by any of said material which may be present in thesample.

The present invention enables the rapid scanning of a surface coatedwith components from a sample to determine their presence and also ifnecessary their optical properties. The system is particularly suitedfor carrying out the automatic inspection of samples with a highthroughput. Moreover, provision of address information in or on thesubstrate enables the precise position of the electromagnetic radiationbeam on the surface to be determined which in turn allows the accuratemapping of optical data, corresponding to attached material, to thesurface. This enables regions of interest on the surface to be easilyand quickly relocated.

The present invention is suited to carrying out ELISA where the specificantigen is coated onto the surface of the substrate. The surface is thenexposed to the analyte and subsequently the specific enzyme and theresulting sample scanned to detect and quantify the enzyme linked to thesurface. The system is also suited to carrying out histological analysisand to the quantitative study of gels run using electrophoresis.

Preferably, the electromagnetic radiation is light, e.g. infra-red,visible or ultra-violet.

According to a third aspect of the present invention there is provided asystem for automatically carrying out an optical inspection of a sampleto determine whether or not the sample comprises material whichinterferes with incident electromagnetic radiation, the systemcomprising;

a substantially planar substrate having a surface for supporting thesample;

a source of electromagnetic radiation for providing a beam ofelectromagnetic radiation;

means arranged on one side of the substrate for scanning the beam acrossthe surface of the substrate;

a first detector for detecting electromagnetic radiation reflected fromthe substrate and the sample;

a second detector for detecting electromagnetic radiation passingthrough the substrate and the sample; and

control means coupled to the first and second detectors and for causingsaid beam to scan the surface of the substrate in dependence upon one orboth of the outputs of the detectors and for detecting the presence ofsaid components.

In a preferred embodiment of the above second aspect of the presentinvention the control means is arranged to determine the differencebetween output signals provided by said first and second detectors,which are representative of the signals detected, for the purpose ofdetecting said material without signal artifacts arising from, forexample, dirt present on the side of the substrate opposite the supportsurface. The substrate may be provided with distributed address meansfor modulating the light beam with digitally encoded positioninformation indicative of the area currently being scanned by the lightbeam, one or other of the detectors being arranged to decode thereceived light signal to determine the address of the location on whichthe light beam is incident.

According to a fourth aspect of the present invention there is provideda system for automatically carrying out an optical inspection of asample to determine whether or not the sample comprises material whichinterferes with incident electromagnetic radiation, the systemcomprising:

a disc comprising a plastic base layer on the upper surface of which isformed a plurality of perturbations, for interfering with incidentelectromagnetic radiation, representing digitally encoded data, and asurface for supporting the sample;

disc reading apparatus including a source of electromagnetic radiationfor providing a beam of electromagnetic radiation, scanning means forscanning the beam across the upper surface of the disk, and anelectromagnetic radiation detector for detecting radiation reflectedfrom and/or transmitted through the disk and said sample components; and

means for rotating the disc about an axis substantially perpendicular tosaid beam,

wherein, in addition to being modulated by information digitally encodedonto the disc, the beam is additionally modulated by any of saidmaterial which is attached to the support surface of the disc.

Preferably, said electromagnetic radiation is visible light althoughinfra-red or ultra-violet radiation may be suitable.

Preferably, the disc comprises a lower layer of transparent plastic onthe surface of which is impressed, or otherwise produced, said digitalinformation. This surface is coated with a partially reflective layer,for example of aluminium, which in turn may be covered by a furtherlayer of transparent plastic.

In an embodiment of the above fourth aspect of the invention the uppersurface of the disc is provided with a 3D surface topology arranged toprovide growth and attachment cues for cells grown on the surface. Forexample, the surface may be provided with a rectangular grating forcausing cells to align in a chosen direction. Alternatively, growth andattachment cues may be provided by chemical patterning of the surface,e.g. using fibrenectin, produced, for example, using photolithography.

In another embodiment of the above fourth aspect of the presentinvention the upper surface of the disc is coated with a gel suitablefor carrying out electrophoresis on proteins, DNA etc. In order to runthe gels radially, a first electrode may be provided at the centre ofthe disc with a second electrode being provided around the periphery ofthe disc. A well may be formed in the gel into which the analyte can beplaced.

In order to calibrate a system embodying the present invention, the discmay be provided with a calibration track, e.g. a series of 256 greylevels. These levels may be printed onto the surface of the track usinga ink jet printer.

According to a fifth aspect of the present invention there is provided asubstrate for use in a system which is arranged to carry out an opticalinspection on the substrate to determine whether or not material whichinterferes with incident electromagnetic radiation is present on asurface of the substrate, the substrate including a preformedcalibration scale which enables calibration of said system.

Preferably, the calibration scale is a series of graded grey regionswhich reflect or transmit light to varying degrees. This scale may beprinted on a surface of the substrate using an ink jet printer.

According to a sixth aspect of the present invention there is providedapparatus for conducting an optical inspection of a biological,chemical, or biochemical sample supported on a substrate, the apparatuscomprising;

means for supporting a substrate and for rotating the substrate about anaxis substantially perpendicular to the substrate;

a source of electromagnetic radiation for providing a beam ofelectromagnetic radiation;

drive means for moving the radiation source over the mounted sample in adirection having a component radial to said axis so that in combinationwith the means for rotating the substrate the radiation beam can bescanned over the substrate; and

detector means for detecting radiation reflected from or transmittedthrough the substrate and sample and for providing an output signalcorresponding to the detected radiation.

For a better understanding the present invention and in order to showhow the same may be carried into effect embodiments of the inventionwill now be described, by way of example, with reference to theaccompanying drawings, in which:

FIG. 1 shows a diagrammatic view of a first embodiment of the presentinvention;

FIG. 2 shows a cross-sectional view of a part of a disc for use with theembodiment of FIG. 1, drawn to a larger scale;

FIG. 3 shows a detailed diagrammatic side elevational view of a secondembodiment of the present invention;

FIGS. 4 (A) to (C) illustrate graphs of outputs from detectors D1 and D2shown in FIG. 3;

FIG. 5 shows a schematic diagram of a control system of the embodimentof FIG. 4;

FIG. 6 shows a diagrammatic view of a third embodiment of the invention;and

FIG. 7 shows a schematic diagram of a control system of the embodimentof FIG. 6.

As discussed above, it is desirable to be able to optically scan asurface to which material is attached for the purpose of quantitativeanalysis of the material, or of a sample from which the material isderived or extracted. FIG. 1 illustrates in simplified form a systemwhich enables this to be achieved. The system uses a circular disc 1(although any other suitable shape of disc may be used) which compriseslower and upper layers of transparent plastic material 2,3 which providethe disc with smooth upper and lower surfaces. Sandwiched between thetwo plastic layers is a thin layer of metal 4 which provides a lightreflecting surface. The plastic may be of any suitable material suchthat the material to be optically analysed can be attached to the uppersurface of the disc in the same way in which it would be attached to anyconventional substrate.

If the system is used to carry out ELISA, the appropriate antibody isbound to the upper surface of the disc (this may require somepre-preparation of the surface). The surface is then exposed to thesample to be tested, e.g. blood plasma, in order to bind any antigens inthe sample to the antibodies. The surface is then washed to remove anyexcess, unbound, material and exposed to the appropriateenzyme-conjugated antibodies 5 which attach to the bound antibodies. Thebound enzymes 5 can be visualised by reacting them with a substrate toproduce a coloured precipitate. The precipitate presents a multiplicityof minute opaque patches over the upper surface of the disc. It will beapparent that the system is equally applicable to other types of assaywhich produce a colour, or other light interfering, change.

The disc is mounted on a rotatable shaft 6 which is driven by a drivemeans (not shown in FIG. 1) causing the disc to rotate. An optical block7 is mounted above the disc and is movable along a substantially lineartrack. The optical block 7 comprises a laser diode 8 which produces abeam of coherent light 9 which is collimated and focused on to thesurface of the disc 1 by a lens arrangement 10. The optical block alsocomprises a detector 11 for detecting light reflected from the surfaceof the metal layer within the disc. The lens arrangement 10 includes apolarising prism 12 which allows only vertically polarised light to passtherethrough and a quarter wave plate 37 which causes light to berotated by 45°.

In operation, the disc is rotated by the drive means relative to theoptical block. With the block stationary the light beam produced by thelaser diode travels around a circular track of the disc. By moving theoptical block along its linear track it is possible to scan the laserbeam around any selected circular track of the disc. In areas of thedisc surface where no light absorbing material is present, light passesthrough the upper plastic layer, is reflected from the metal layer, andtravels back to the optical block, through the upper plastic layer.Light entering the optical block encounters first the quarter wavelengthplat 37, which rotates the light by a further 45°, and then thepolarising prism which, because the polarization of the reflected lighthas been rotated by 180°, causes the light to be redirected at rightangles towards the detector.

When the light beam is incident upon areas of the disc surface wherelight absorbing material is present, light is absorbed by the material,both upon entry to and exit from the upper plastic layer of the disc,and the light received by the detector 11 is substantially reduced.

The detector 11 is coupled to a data analysis and logging system whichstores the output of the detector. This system may store the output as acontinuous analogue signal or as discrete digital samples whichrepresents a reduced resolution image of the surface. Assuming thelatter, the sampling rate may be varied to fit the data storage capacityavailable.

The optical, mechanical and electrical means so far described forimplementing an analyte detector are substantially as conventionallyused for reading data from compact discs. One such conventional systemis described in the text book ‘Digital Audio and Compact DiscTechnology’, 2nd edition, Edited by Luc Baert et al (Sony Service CentreEurope), Newnes, 1994.

The system of FIG. 1 is adequate for obtaining an image of the discsurface, or a portion of that surface when the actual location of theportion itself is no significance. However, it may be desirable to beable to scan a selected area of the disc surface, for example where anELISA has been carried out only in that region, or when it is desired tolook again at a specific region of interest.

Conventional compact discs encode digital information in an intermediateregion of the disc by producing a series of perturbations 13 (e.g. bumpsor pits) on the upper surface of a lower plastic layer 14 andsubsequently coating this surface with a reflective layer 15 such as athin layer or aluminium. The reflective layer is then covered with alayer of transparent plastic 16 which provides protection for theintermediate layer (FIG. 2).

It is possible to use this same technique to digitally encode positioninformation into the disc of FIG. 1. Assuming that the position originis at the centre of the disc, the first position on the innermostcircular track or spiral can be imprinted with the position code zero(in binary representation). Position codes can be imprinted at discretepositions (e.g. every 2 to 3 μm or at any other appropriate interval)around that innermost track incrementing by one between each position.Similarly, the codes are incremented from track to track. Alternatively,address information may be distributed according to a track/sectorarrangement in the same way in which servo-codes are encoded ontomagnetic floppy and hard disks.

Over areas of the surface of the disc which are not covered by opaquematerial, light incident on the upper surface of the disc is transmittedthrough the upper transparent plastic protective layer and is incidentupon the reflective layer. This light is reflected from the reflectivemetal coating except where that coating lies over a bump which causesincident light to be dispersed and not directly reflected back to thedetector. The output from the detector can therefore be demodulated todetermine the address of the disc surface which is currently beingscanned.

Over areas of the disc surface where opaque material causes the incidentlight beam to be substantially absorbed rather than reflected, noposition information will be present at the output of the detector.However, if the density of the opaque material is relatively low thegaps in the address information may not be significant.

In situations where address information is more critical however, a moresophisticated system can be utilised for which the optics are shown inFIG. 3 and which makes use of discs having address information digitallyencoded and distributed over an intermediate layer as described above.This system also makes use of the fact that the reflective layer can bemade to transmit a significant proportion of the incident light (e.g.40%). As with the system of FIG. 1, the system of the second embodimentincludes a shaft 17 on which the disc 18 is mounted and which causes thedisc to rotate and means for moving the optics along a linear trackrelative to the upper surface of the disc. The rotation and displacementmeans are now shown in FIG. 2 for simplicity.

The optical system of FIG. 3 comprises a light source 19, which may befor example a semi-conductor laser or a light emitting diode, arrangedbeneath the disc. The output beam 20 of the light source is directed toan optical axis 20 a to a polarising prism (a beam splitter) 21 whichallows only light of a given polarisation to pass, i.e. only the lightreceived directly from the laser. The transmitted light is then incidentupon a first lens 22 which is arranged to focus light onto the lowersurface 23 of the reflective layer within the disc. A fraction of thelight incident upon the compact disc is transmitted through thereflective layer and exits from the upper surface of the disc. Anymaterial attached to the upper surface will interfere with light exitingthe disc.

Transmitted light which is not interfered with is received by acollimation lens 24, focused onto the upper surface of the disc, whichdirects the received light onto a partially transparent mirror 25 whichin turn allows a fraction of the incident light to pass therethroughwhilst causing the remainder to be reflected at right angles. Lightpassing directly through the partially transparent mirror is incidentupon a further lens 26 which focuses the light onto the detectionsurface of a detector D2. Light reflected at right angles by the mirror25 is incident upon a lens 27 which focuses light onto a detector D3.

As already described, a fraction of the light incident on the reflectivelayer within the disc is reflected back towards the first lens 22 whichacts as a collimation lens directing light back to the polarising prism21. The reflected light is now horizontally polarised and is reflectedfrom the polarising prism at right angles to the optical axis. Thisreflected light is received by a fourth lens 28 which focuses receivedlight onto a detector D1.

Light reflected by the reflective layer will be modulated with theinformation digitally encoded into the disc so that the output from thedetector D1 will be similarly modulated. As this light does not exitfrom the upper surface of the disc it will not be interfered with bymaterial attached to the upper sample support surface of the disc andaddress information can be determined from the output of D1 with minimalerror.

Although not shown in FIG. 3 the optical block situated below the discalso incorporates tracking optics which enables the correct tracking ofthe disc tracks in a similar way to that used in conventional compactdisc players. The tracking optics comprise a diffraction grating,located in this embodiment at plane 37 in FIG. 3, which splits theoutput from the laser into three parallel beams which are subsequentlyfocused by the first lens to provide three slightly spaced-apart spots.The spacing between these spots is such that when the central spot isdirectly over the centre of one track the other two spots lie on eitherside of that track. The detector D1 actually comprises three adjacentdetectors which receive reflected light and the spacing of which isequivalent to that between the beam spots. In order to align the lasercorrectly, the laser position is adjusted until the output from thecentre detector is maximum and the outputs from the two side detectorsis a minimum. A feedback control system is used to maintain the correcttracking.

The output provided by detector D2 is modulated with the digital addressinformation encoded onto the disc and, provided that no light absorbingmaterial is attached to the upper surface of the disc, is substantiallyof the form of the output of detector D1, i.e. the ratio of the outputsignals of D1 and D2 will be constant. However, if light absorbingmaterial is present on the upper surface of the disc this will interferewith light transmitted through the reflective layer and the output fromdetector D2 will drop whilst that from D1 will remain constant. Theratio of the output signals of D1 and D2 will change accordingly. If thematerial attached to the surface of the disc is reflective, e.g. goldlabelled, the output of D1 will rise whilst that of D2 will fall whenthe light beam scans the material. The ratio of D1 and D2 will indicatethe presence of such material.

FIG. 4 illustrates the case where the bound material is absorbent butnot reflective and shows at (A) a cross-section taken through typicaldisc to the surface of which a stained cell 29 is attached. Thereflective layer beneath the support surface is encoded with the digitaladdress 10101. As the beam scans along the track the ratio between theoutput signals of detectors D1 and D2 (FIG. 4B) remains constant wherethe upper surface is not covered by the cell. In the central area,however, where the cell is shown covering the upper surface, the signalproduced by detector D2 falls so that the ratio (FIG. 4C) of the signalsproduced by D1 and D2 similarly drops.

FIG. 5 shows a block diagram of a system for controlling the embodimentof FIG. 3 with the flow of data through the system being indicated byarrows. The analogue outputs from detectors D1 and D2 are received by anintegrated circuit 30 which determines the ratio of the two outputs.This ratio is then converted to digital form by an analogue to digitalconverter 31 and transmitted to a bitstream generator 34 for compressionusing bitstream modulation. The output from detector D1, whichrepresents the digitally encoded address information, is alsotransmitted to an address bitstream generator 33 for compression. Thetwo channel bitstream data is received by a bitstream merge and displayunit which processes the data for storage and for display.

In order to provide more stringent measure of the variations in theintensity of light transmitted through the disc the detector D3 isprovided (although this is optional) which receives light from thepartially transparent mirror through the aperture 53, lens 27 andpinhole arrangement 35. This arrangement effectively reduced the area ofthe disc surface from which light is received by the detector D3 andalso reduces the depth of focus. If the output of detector D2, or theratio D1:D2, exceeds a predetermined threshold the output of detector D3can be used to increase the resolution with which the surface of thedisc is viewed. The use of detectors D2 and D3 in combination preventsthe likelihood of the detector D2 producing errors if the system usedonly detector D2. D3 may alternatively provide a second type of detectorfor detecting for example fluorescent light emitted by material attachedto the surface of the disc.

FIG. 6 shows a further embodiment of the invention in which absoluteposition information can be determined, although the accuracy of thisinformation may be somewhat less than that provided by the embodiment ofFIGS. 4 and 5. However, the disc construction is considerablysimplified.

The optical inspection system has a ‘U’ shaped arm 36 with a lightsource 52 and a detector 38 attached to the upper and lower ends of thearm respectively. The source and detector are connected to a lasercontroller 39 and a buffer 40, the latter being arranged to transferdetected signal data to a personal computer 41 via an analogue todigital converter 42 and a data store 43.

The disc 44 upon which the sample to be inspected is attached orsupported is mounted on a rotatable spindle 45 which lies parallel tothe bight 46 of the arm 36. The spindle 45 is driven be a spindle motor47. The optical axes of the light source 37 and detector 38 are alignedwith one another along the axis A—A.

The arm 36 is coupled to a stepper motor 48 which precisely rotates thearm in a plane parallel to the plane of the disc 44 such that, incombination, rotation of the arm and of the disc allows the lightsource/detector arrangement to be scanned across the entire useablesurface of the disc. The stepper motor 48 is controlled by a motioncontroller 49, which in turn is controlled by the computer 41, such thatthe relative position of the spindle 45 can be determined to within anaccuracy of 6 μm.

The disc is of a completely transparent material but is provided with ablack bar 50 around a portion of its upper peripheral surface. The bar50 acts as an angular calibration marking for the inspection system.When it is required to inspect a disc, the arm 36 is moved to anoutermost “home” position, where the light source/detector arrangementis situated off the disc 44. In this position, the laser and detectorare calibrated to ensure a constant, maximum output signal. The arm 36is then rotated to move the light source/detector arrangement towardsthe disc.

When the edge of the disc is detected, the arm is held stationary untilthe calibration marking 50 interrupts the beam. The leading edge of themarking 50 provides an origin to which the angular position of thedetector can be referenced whilst the edge of the disc provides anorigin for the radial position. Due to the accuracy of the stepper motor48 and the spindle motor 46, it is then possible to precisely determinethe position of the light source/detector arrangement relative to thedisc.

In the system of FIG. 6, the disc 44 comprises a plurality of wells orindentations 51 formed in its upper surface. The wells contain thesample to be inspected and are filled, for example, by microtitration.Rather than scan the whole surface of the disc, the personal computermay be arranged to step the light source/detector arrangement over thedisc surface from one well to another. This is enabled by the preciseposition information obtained from the calibration marking and the discedge. FIG. 7 shows a flow diagram of the control process for thissystem.

The system of FIG. 6 may be modified so that the light source 37 and thedetector 38 are both arranged on the same side of the disc, with thedisc being provided with a reflective coating on or beneath the surfaceon which the sample is supported. In this arrangement the detectordetects light reflected from the reflective coating. The two mainadvantages of the arrangement are that the surface of the disc whichdoes not support the sample may be safely handled, as it does not lie inthe light transmission path, and that the signal to noise ratio of theoptical inspection process may be increased because light will have topass through a sample twice in travelling from the source to thedetector.

It will be apparent that various modifications may be made to the abovedescribed embodiments without departing from the scope of the invention.For example, the support surface of the disc may be scanned withinfra-red or ultra-violet radiation rather than visible light. It isalso possible to scan the surface with radiation which excitesfluorescence in material attached to the surface and to use the detector(D2 or D3) arrangement to detect light at the emission wavelength.

It is also possible to construct the disc in such a way that the supportsurface is internal to the disc and is not the upper surface of thedisc. This may provide the advantages that the sample is not damaged byhandling and that a precise volume of sample may be analysed. To enablethe system to be used for running gels (e.g. to identify proteins, DNAetc), an appropriate gel may be provided on the upper surface of thedisc. Electrodes for applying a potential across the gel may be formedintegrally therewith or may be printed, or otherwise deposited, on theupper surface. The electrodes may be spaced radially orcircumferentially. Pits may be provided in the gel into which thematerial to be run can be placed.

Another modification to the above described embodiments involvesreplacing the light detector with a photo-diode array, e.g. a CCD array.A preferred form of array is a linear array extending radially withrespect to the disc. The light source would take the form of a laserline generator arranged to generate a radially extending line of lightaligned with the diode array. Some degree of optical magnification maybe incorporated between the source and the generator to allow theresolution of the system to be varied. After each rotation of the disc,the source/detector arrangement would be stepped inwardly by the lengthof the laser line. The advantages of this arrangement are high speed andhigher resolution.

What is claimed is:
 1. An optical disc for use in conducting an opticalinspection of a biological, chemical or biochemical sample inassociation with an optical reader capable of scanning and readingoptical discs with a beam of light, said disc comprising: an opticallytransparent substrate having a semi-reflective layer which reflects aportion of said beam of light to form a reflected beam and transmits aportion of said beam of light to form a transmitted beam, saidsemi-reflective layer including optically readable encoded informationto be read by said reader for controlling the scanning of said readerrelative to said disc, said encoded information providing modulation ofsaid reflected beam; and a sample support surface positioned to bescanned by said reader and on which said biological, chemical orbiochemical sample may be located, for optical inspection with saidtransmitted beam.
 2. An optical disc according to claim 1 in which saidencoded information and said sample on said support surface are inoptical alignment with respect to said beam of light.
 3. A discaccording to claim 1 in which said optically readable encodedinformation is in the form of a circular track or a spiral track.
 4. Anoptical disc according to any of the preceding claims 1 through 3 inwhich said encoded information is located in at least an intermediateregion of said disc.
 5. An optical disc according to any of thepreceding claims 1 through 3 in which said disc includes a biological,chemical or biochemical material attached to said sample supportsurface.
 6. An optical disc according to claim 5 in which said materialattached to said sample support is coloured, reflective or fluorescent.7. An optical disc according to claim 1 which comprises a gel andelectrodes for applying a potential across said gel.
 8. A system forconducting optical inspection of a biological, chemical or biochemicalsample comprising: (A) a disc according to claim 1; and (B) an opticaldisc inspection assembly including: (a) a radiation source for providingat least one beam of electromagnetic radiation; (b) a detection systemcomprising one or more detectors for detecting radiation reflected fromand transmitted through said semi-reflective layer.
 9. A systemaccording to claim 8 in which said radiation source is located relativeto said disc so that said sample support surface is located between saidradiation source and said semi-reflective layer.
 10. A system accordingto claim 8 in which said radiation source is located relative to saiddisc so that said semi-reflective surface is located between saidradiation source and said sample support surface.
 11. A system accordingto claim 10 in which said detection system comprises two detectorswherein one of said two detectors is located on the same side of saiddisc as said radiation source and the other of said two detectors islocated on the side of said disc opposite said radiation source.
 12. Asystem according to claim 11 in which said detection system furthercomprises a third detector located on the side of said disc oppositesaid radiation source.
 13. A system according to claim 8 in which saiddetection system comprises a video monitor for viewing the results ofsaid optical inspection.
 14. A system according to claim 8 in which saiddisc comprises a gel and electrodes for applying a potential across saidgel.
 15. A method of conducting an optical inspection of a biological,chemical or biochemical sample employing a disc adapted to be read by anoptical reader, comprising the steps of: providing such a sampleassociated with a disc according to claim 1; conducting an opticalinspection of said sample using an optical reader; and reading saidencoded information with said reader.
 16. The method of claim 15 inwhich said steps of conducting an optical inspection and said step ofreading encoded information each include the substeps of using quarterwave light reflected from said disc as part of said conducting andreading steps.
 17. The method of claim 15 in which said encodedinformation is optically interrupted by the presence of said sample andsaid optical inspection of said sample is accomplished sequentially tothe reading of said encoded information.
 18. A method according to claim15 in which said conducting includes providing an optical image of saidmaterial.
 19. A method according to claim 15 in which said opticalinspection includes directing a beam of radiation onto said sample toproduce detectable radiation which is reflected from and/or transmittedthrough said sample.
 20. A method according to claim 19 in which onlydetectable radiation which is reflected from said disc is measured. 21.A method according to claim 19 in which detectable radiation which isboth reflected from and transmitted through said disc is measured.
 22. Amethod according to claim 15 in which said sample support surface isinternal to said disc.